The long-term goal of this project is to develop a vaccination system for humans and animals, which can be administered orally and is multi-valent protecting against the major pathogens of the species. Our prior published results using a mouse-influenza model has shown that a modified vaccinia virus Ankara (MVA) recombinant vaccine has the potential to meet this goal. We propose to use a swine influenza model with which we have some experience. This model offers both immediate commercial value (influenza is a significant problem for the swine industry) and basic research value (the pig is a good experimental model to study potential oral immunization strategies for man). In Phase 1 we expect to demonstrate that when the vaccine is administered directly into the jejunum, it stimulates both serum IgG and mucosal IgA antibody and prevents infection from a homologous swine influenza virus. In Phase 2 we will develop an enteric coated, orally administered recombinant vaccine in order to avoid destruction of the vaccine virus by stomach acid and bile and to demonstrate its immunogenicity and efficacy. There should be a significant market for this vaccine because there are 60-80 million pigs raised annually in the U.S. PROPOSED COMMERCIAL APPLICATIONS: Successful completion of Phase I is expected to provide MVA viruses that will be formulated for delivery as oral vaccines and tested - first in pigs and then in animal models for human diseases. A Phase II SBIR grant would provide a portion of the funding for this follow-on work. Several other companies have expressed an interest in co-development agreements once the company demonstrates the ability to induce an effective immune response to an MVA virus vaccine.